In order to immunologically correct aberrant regulation of lymphopoiesis which leads to cancers such as lymphomas, myelomas and leukemias, an understanding of normal regulatory events is needed. This project is designed to investigate changes which take place as stem cells differentiate into clones of functional lymphoid cell populations. The experimental approaches will make use of an in vitro system to elucidate the steps of maturation and the regulatory mechanisms which direct biophysically purified precursor cells in their development into functional helper, effector, memory and suppressor lymphocytes. Stem cell or precursor cell surface changes will be followed using membrane probes to correlate molecular modifications that arise during differentiation with lymphoid acquisition of functional capacity. Selective maturation and induction of functional lymphocyte populations in vitro could then be used to repair immunodeficiences or to provide appropriate numbers of antigen-specific lymphocytes that are capable of restricting growth of neoplastic tissue in situ. Memory cells could be induced which would supply backup numbers of hyperactive effector of surveillant lymphocytes.